000226922 001__ 226922
000226922 005__ 20181203024620.0
000226922 0247_ $$2doi$$a10.1111/eci.12708
000226922 022__ $$a0014-2972
000226922 02470 $$2ISI$$a000393880500002
000226922 037__ $$aARTICLE
000226922 245__ $$aAlamandine abrogates neutrophil degranulation in atherosclerotic mice
000226922 260__ $$bWiley-Blackwell$$c2017$$aHoboken
000226922 269__ $$a2017
000226922 300__ $$a12
000226922 336__ $$aJournal Articles
000226922 520__ $$aBackground Neutrophil-mediated inflammation was recently identified as an active contributor to athero-progression. Therapeutic strategies inhibiting neutrophil degranulation or recruitment were hypothesized to positively impact on plaque vulnerability. In this study, we investigated whether treatment with the recently discovered agonist of the Mas-related G-coupled receptor type D (MrgD) alamandine would impact on neutrophil degranulation in vivo and in vitro. Materials and methods Fifteen-week-old ApoE(-/-) mice were fed with a Western-type diet for an additional 11 weeks. After the first 2 weeks of diet, mice were surgically implanted with a carotid 'cast' device that alters the blood shear stress and induces different carotid plaque phenotypes. During the last 4 weeks before euthanasia, mice were randomly assigned to subcutaneously receive vehicle (NaCl 0.15 M) or alamandine (24 lg/kg/h) by micropump. For in vitro experiments, neutrophils were obtained after thioglycollate intraperitoneal injection in ApoE(-/-) mice. Results Treatment with alamandine was well-tolerated, but failed to affect lipid, macrophage, neutrophil or collagen content within carotid and aortic root plaques. Also, treatment with alamandine did not affect Th-cell polarization in lymphoid organs. Conversely, alamandine administration was associated with a reduction in serum levels of neutrophil granule enzymes, such as MMP-9 and MPO as well as MMP-9 content within aortic root plaques. In vitro, preincubation with alamandine dose-dependently abrogated PMA-induced neutrophil degranulation of MMP-9 and MPO. Conclusion These results suggest that treatment with the MrgD agonist alamandine led to a reduced release of neutrophil granule products, potentially interfering with pro-atherosclerotic neutrophil activation.
000226922 6531_ $$aAtherosclerosis
000226922 6531_ $$aMas receptor
000226922 6531_ $$aneutrophils
000226922 700__ $$uUniv Geneva, Div Cardiol, Dept Med Specialties, Fdn Med Res, 64 Ave Roseraie, CH-1211 Geneva, Switzerland$$aDa Silva, Analina R.
000226922 700__ $$uUniv Genoa, Sch Med, Dept Internal Med, Clin Internal Med 1, 6 viale Benedetto 25, I-16132 Genoa, Italy$$aLenglet, Sebastien
000226922 700__ $$uUniv Genoa, Sch Med, Dept Internal Med, Clin Internal Med 1, 6 viale Benedetto 25, I-16132 Genoa, Italy$$aCarbone, Federico
000226922 700__ $$uUniv Geneva, Div Cardiol, Dept Med Specialties, Fdn Med Res, 64 Ave Roseraie, CH-1211 Geneva, Switzerland$$aBurger, Fabienne
000226922 700__ $$uUniv Geneva, Div Cardiol, Dept Med Specialties, Fdn Med Res, 64 Ave Roseraie, CH-1211 Geneva, Switzerland$$aRoth, Aline
000226922 700__ $$uUniv Genoa, Sch Med, Dept Internal Med, Clin Internal Med 1, 6 viale Benedetto 25, I-16132 Genoa, Italy$$aLiberale, Luca
000226922 700__ $$uUniv Genoa, Sch Med, Dept Internal Med, Clin Internal Med 1, 6 viale Benedetto 25, I-16132 Genoa, Italy$$aBonaventura, Aldo
000226922 700__ $$uUniv Genoa, Sch Med, Dept Internal Med, Clin Internal Med 1, 6 viale Benedetto 25, I-16132 Genoa, Italy$$aDallegri, Franco
000226922 700__ $$0240635$$g106482$$uEcole Polytech Fed Lausanne, Inst Bioengn, Route Cantonale, CH-1015 Lausanne, Switzerland$$aStergiopulos, Nikolaos
000226922 700__ $$uUniv Fed Minas Gerais, Dept Physiol & Biophys, Belo Horizonte, MG, Brazil$$aSantos, Robson A. S.
000226922 700__ $$uUniv Geneva, Div Cardiol, Dept Med Specialties, Fdn Med Res, 64 Ave Roseraie, CH-1211 Geneva, Switzerland$$aMach, Francois
000226922 700__ $$uEcole Polytech Fed Lausanne, Inst Bioengn, Route Cantonale, CH-1015 Lausanne, Switzerland$$aFraga-Silva, Rodrigo A.
000226922 700__ $$aMontecucco, Fabrizio$$uUniv Genoa, Sch Med, Dept Internal Med, Clin Internal Med 1, 6 viale Benedetto 25, I-16132 Genoa, Italy
000226922 773__ $$j47$$tEuropean Journal Of Clinical Investigation$$k2$$q117-128
000226922 909C0 $$xU11843$$0252351$$pLHTC
000226922 909CO $$pSTI$$particle$$ooai:infoscience.tind.io:226922
000226922 917Z8 $$x206205
000226922 937__ $$aEPFL-ARTICLE-226922
000226922 973__ $$rREVIEWED$$sPUBLISHED$$aEPFL
000226922 980__ $$aARTICLE